【摘要】：目的：探討急性期精神分裂癥患者多巴胺D2受體及其下游細(xì)胞內(nèi)信號(hào)轉(zhuǎn)導(dǎo)通路關(guān)鍵基因PI3K、AKT在外周血白細(xì)胞中的mRNA表達(dá)水平，并分析其與精神病性癥狀、糖脂代謝的關(guān)系，研究其在精神分裂癥診療過(guò)程中的價(jià)值。 方法：于2011年7月至2012年9月間在無(wú)錫市精神衛(wèi)生中心入組急性期精神分裂癥住院患者24例，慢性期長(zhǎng)期住院病人19例，正常對(duì)照21例。以real-timeRT PCR的方法檢測(cè)多巴胺受體D2（dopamine receptor D2，DRD2）、絲氨酸/蘇氨酸蛋白激酶Akt（serine/threonine protein kinase Akt， AKT）、磷脂酰肌醇3-激酶（Phosphoinositide3-kinase，PI3K）基因在外周血白細(xì)胞中的信使核糖核酸（Messenger RNA，mRNA）表達(dá)水平，同時(shí)檢測(cè)其血漿糖脂代謝的相關(guān)生化指標(biāo)，并以陽(yáng)性和陰性癥狀量表（Positive and Negative Syndrome Scale，PANSS）評(píng)定患者的精神病性癥狀。分析急性期精神分裂癥患者DRD2、AKT、PI3K基因在外周血白細(xì)胞中的mRNA表達(dá)水平與其精神病性癥狀、糖脂代謝的關(guān)系。 結(jié)果：在急性期組與正常對(duì)照組的血清表達(dá)量中，DRD2（F=102.73，P=0.00）及PI3K(F=2.30，P=0.11)均存在顯著差異，將DRD2與PI3K的慢性期與正常對(duì)照組的對(duì)比，，則不存在顯著差異。AKT的急性期組與正常對(duì)照組不存在顯著差異，慢性期組與正常對(duì)照組有顯著差異（F=16.71，P=0.00）。在糖代謝方面，急性期組的空腹胰島素（t=4.25，P=0.00）和餐后2小時(shí)胰島素（t=3.10，P=0.01）都與正常對(duì)照組有著顯著差異。而空腹血糖、餐后2小時(shí)血糖以及空腹C肽和餐后2小時(shí)C肽等指標(biāo)的急性組與正常對(duì)照組之間無(wú)差異。而急性期的HOMA-IR與PI3K、與AKT以及DRD2之間的表達(dá)未見(jiàn)明確的相關(guān)性。同時(shí)，急性期的HOMA-IR與正常人的值相比較，也沒(méi)有明顯差異。在脂代謝方面，可以看到四項(xiàng)急性期組的指標(biāo)只有甘油三酯與正常對(duì)照組沒(méi)有顯著的差異，另外三項(xiàng)關(guān)于脂代謝的總膽固醇（t=4.00，P=0.00）、HDL（t=7.77，P=0.00）及LDL（t=2.62，P=0.01）在急性期組與正常組之間都有著顯著性差異。在PANSS量表的得分與基因表達(dá)量方面，可以明確發(fā)現(xiàn)，量表的得分與基因的表達(dá)不存在明確的線性相關(guān)。 結(jié)論：急性期精神分裂癥患者外周血的PI3K、AKT及DRD2基因表達(dá)水平都與正常人群存在著顯著差異。但其基因的表達(dá)量與患者所表現(xiàn)出來(lái)的癥狀并無(wú)明確的相關(guān)關(guān)系。此外，精神分裂癥病人在糖脂代謝方面均存在一定的異常，這提示著DRD2-PI3K-AKT信號(hào)通路在精神分裂癥發(fā)病機(jī)制和糖脂代謝中發(fā)揮重要作用。
[Abstract]:Objective: to investigate the expression of dopamine D2 receptor and its downstream signal transduction pathway gene PI3K,AKT in peripheral blood leukocytes in patients with acute schizophrenia, and to analyze the relationship between the expression of mRNA and psychiatric symptoms, glucose and lipid metabolism. To study its value in the diagnosis and treatment of schizophrenia. Methods: from July 2011 to September 2012, 24 patients with acute schizophrenia, 19 patients with chronic schizophrenia and 21 normal controls were enrolled in Wuxi Mental Health Center. The expression of dopamine receptor D2 (dopamine receptor D2DRD2, serine / threonine protein kinase Akt (serine/threonine protein kinase Akt, AKT), phosphatidylinositol 3-kinase (Phosphoinositide3-kinase,PI3K) gene) in peripheral white blood cells (PBWs) was detected by real-timeRT PCR. At the same time, the related biochemical indexes of plasma glucose and lipid metabolism were detected, and the psychiatric symptoms were assessed by positive and negative symptom scale (Positive and Negative Syndrome Scale,PANSS). To analyze the relationship between the expression of DRD2,AKT,PI3K gene mRNA in peripheral blood leukocytes and psychotic symptoms, glucose and lipid metabolism in patients with acute schizophrenia. Results: in the acute phase group and the normal control group, there were significant differences in the serum expression levels of DRD2 (FG 102.73) and PI3K (FN 2.30 P0. 11). The chronic phase of DRD2 and PI3K was compared with that of the normal control group. There was no significant difference in AKT between the acute phase group and the normal control group, but there was significant difference between the chronic phase group and the normal control group. In terms of glucose metabolism, fasting insulin (tb4.25m) and postprandial insulin (t 3.10g / P0.01) in the acute phase group were significantly different from those in the normal control group. There was no significant difference in fasting blood glucose, postprandial blood glucose, fasting C-peptide and 2-hour postprandial C-peptide between the acute group and the normal control group. However, the expression of HOMA-IR, PI3K, AKT and DRD2 in acute stage was not positively correlated. At the same time, there was no significant difference in HOMA-IR between the acute stage and the normal subjects. In the aspect of lipid metabolism, it can be seen that only triglyceride has no significant difference between the four acute phase groups and the normal control group, and the other three items of total cholesterol (t 4. 00), HDL () and LDL (t 2. 62% P0. 01) are significantly different between the acute phase group and the normal group. In the aspect of PANSS score and gene expression, it is clear that there is no linear correlation between the score and gene expression. Conclusion: the expression levels of PI3K,AKT and DRD2 genes in peripheral blood of patients with acute schizophrenia are significantly different from those of normal controls. However, there was no clear correlation between gene expression and symptoms. In addition, there are some abnormalities in glucose and lipid metabolism in schizophrenic patients, which suggests that DRD2-PI3K-AKT signaling pathway plays an important role in the pathogenesis of schizophrenia and glycolipid metabolism.
【學(xué)位授予單位】：皖南醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類(lèi)號(hào)】：R749.3

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